Does it harm the embryo to thaw it and perform a biopsy on it?

Written by: Jessica Manns, MBMS, BS

Embryos that have been created and frozen (cryopreserved) through IVF can still be biopsied. Though this process is now routinely performed with over 90% success (data is limited and results may vary between clinics), it involves warming (commonly called thawing), biopsying, and refreezing an embryo; the process may come with some risks.

An embryo is thawed by quickly immersing it in a warm medium (fluid) that pushes water into its cells and removes the cryoprotectant (media that was used to freeze it) from the embryo. The embryo is then placed into a culture medium inside a petri dish and is stored in an incubator. This process allows the embryo to safely re-expand to its pre-thaw state over the course of a few hours. Embryos do not develop while they are frozen. In general, over 95% of embryos survive the freezing and thawing procedures. Different manufacturers may have specific instructions for thawing embryos.

After the embryo is thawed, it is given a few hours to re-expand in its culture medium. Once it is re-expanded, the embryo can be biopsied. For this procedure, 5-10 cells are removed from the embryo's trophectoderm (the part of the embryo that ultimately develops into the placenta). This biopsied sample is sent to a genetic testing company, while the embryo is refrozen inside the IVF lab. The freezing process pulls water from the embryo's cells and coats the cells with a cryoprotectant agent. Each manufacturer has its own instructions for freezing embryos.

After about two weeks, the genetic testing company should release the PGT results of your embryo(s). If an embryo is deemed suitable for transfer, it can be thawed a few hours prior to a frozen embryo transfer using the same thawing protocol described above.

Embryos that undergo a thaw, biopsy, and refreeze are exposed to added manipulation compared to embryos that do not undergo these procedures. In each of these processes, there is a risk of damage to some or all of the embryo's cells. An embryo is considered non-viable if over 50% of its cells are degenerate. However, good quality embryos are often not damaged by this process (though it can happen). Poor quality embryos tend to incur more damage during this process since they have less cells to begin with. This is especially true for poor quality embryos that are undergoing a second biopsy (in other words, they were biopsied, frozen, thawed, biopsied again, and frozen again) since a larger fraction of its cells are removed during this process.

While some studies have found reduced clinical pregnancy rates after a thaw, biopsy, and refreeze, other studies have found no differences in these rates. It is best to talk with your doctor about your clinic's success rates with an embryo thaw, biopsy, and refreeze procedure. It's important to know the benefits and risks before making the decision to test your frozen embryos.

Sources:

Repeated freezing and thawing impacts IVF outcomes in PGT-A cycles | Remembryo

Biopsy and refreeze with the Cryotop® Method - Kitazato IVF (kitazato-ivf.com)

Thaw, biopsy and refreeze strategy for PGT-A on previously cryopreserved embryos - PubMed (nih.gov)